This Specialized Program of Research Excellence (SPORE) in Ovarian Cancer is submitted from the Dana-Farber/Harvard Cancer Center (DF/HCC) and combines 5 translational projects, 3 supportive cores, and 2 synergistic programs. Project 1 will examine gene-environmental interactions affecting modifiable exposures, such as anti-inflammatory drug or genital talc use, in combined data from the Nurses' Health Cohort and a large case-control study. Project 2 seeks to identify histology-specific molecular genetic changes in large and well-characterized collections of early-staged tumors using innovative DNA-based technologies coupled with bioinformatics. Project 3 will identify biomarkers of occult ovarian cancers or precursor lesions through proteomic analysis of pre- and post-operative blood and urine specimens from women attending DF/HCC and Cancer Genetics Network Clinics for prophylactic salpingo-oophorectomy. Project 4 will identify genetic pathways associated with paclitaxel and carboplatin drug resistance, building upon exciting cell line work that points towards acquired pathways and transcriptional profiling that seeks to identify intrinsic mechanisms. Project 5 proposes Phase I and II trials to assess the value of two distinct vaccine approaches---one using recombinant vaccinia viruses and another involving dendritic cell and ovarian cancer cell fusions. Projects 1 and 3 satisfy SPORE requirements related to prevention or screening while Projects 2, 4, and 5 address biologic foundations that may translate into interventional strategies. Administrative, Biostatistical, and Tissue Cores are collaboratively structured and will support the aims of current and future projects. A Developmental Research Program will reinforce scientific and technological foundations for the DF/HCC Ovarian Cancer SPORE and maintain the balance and diversity of its projects, while a complementary Career Development Program will increase the number of researchers committed to ovarian cancer and maximize their potential to be leaders. The overall mission of the DF/HCC SPORE is to address the full range of prevention, early detection, and treatment of ovarian cancer.